GRAPHICAL MODELS FOR ZERO-INFLATED SINGLE CELL GENE EXPRESSION

The Annals of Applied Statistics
Andrew McDavidMathias Drton

Abstract

Bulk gene expression experiments relied on aggregations of thousands of cells to measure the average expression in an organism. Advances in microfluidic and droplet sequencing now permit expression profiling in single cells. This study of cell-to-cell variation reveals that individual cells lack detectable expression of transcripts that appear abundant on a population level, giving rise to zero-inflated expression patterns. To infer gene co-regulatory networks from such data, we propose a multivariate Hurdle model. It is comprised of a mixture of singular Gaussian distributions. We employ neighborhood selection with the pseudo-likelihood and a group lasso penalty to select and fit undirected graphical models that capture conditional independences between genes. The proposed method is more sensitive than existing approaches in simulations, even under departures from our Hurdle model. The method is applied to data for T follicular helper cells, and a high-dimensional profile of mouse dendritic cells. It infers network structure not revealed by other methods; or in bulk data sets. An R implementation is available at https://github.com/amcdavid/HurdleNormal.

References

Feb 2, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Esther C de JongMartien L Kapsenberg
May 31, 2007·The Journal of Experimental Medicine·Melissa L PrecopioRichard A Koup
Oct 2, 2007·BMC Bioinformatics·Florian Markowetz, Rainer Spang
Jan 28, 2010·Blood·Natascha Hermann-Kleiter, Gottfried Baier
Mar 17, 2010·Nature Methods·Kevin A JanesJoan S Brugge
Jul 4, 2012·The Journal of Experimental Medicine·Cindy S MaStuart G Tangye
Jan 31, 2013·Genome Biology·Jong Kyoung Kim, John C Marioni
Nov 28, 2014·Nucleic Acids Research·UNKNOWN Gene Ontology Consortium
Mar 1, 2012·Journal of the Royal Statistical Society. Series B, Statistical Methodology·Robert TibshiraniRyan J Tibshirani
May 26, 2015·Nature Biotechnology·Lin LinRaphael Gottardo
Jul 1, 2012·Statistica Sinica·Noah Simon, Robert Tibshirani
Oct 7, 2015·Trends in Plant Science·Yupeng LiScott A Jackson
Mar 1, 2015·Biometrika·Shizhe ChenAli Shojaie
Aug 8, 2019·The Annals of Applied Statistics·Andrew McDavidMathias Drton

❮ Previous
Next ❯

Citations

Dec 30, 2020·BMC Bioinformatics·Min Jin HaChristine B Peterson
Aug 8, 2019·The Annals of Applied Statistics·Andrew McDavidMathias Drton
Apr 19, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Maria KuksinLoïc Verlingue
Jun 8, 2021·Computational and Structural Biotechnology Journal·Monica Steffi MatchadoMarkus List

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

IEEE Transactions on Nanobioscience
Genevera I Allen, Zhandong Liu
IEEE Transactions on Neural Networks and Learning Systems
Feihu HuangSheng-Jun Huang
Journal of Computational and Graphical Statistics : a Joint Publication of American Statistical Association, Institute of Mathematical Statistics, Interface Foundation of North America
Hyonho ChunHongyu Zhao
International Journal of Data Mining and Bioinformatics
Youngsoon KimMingon Kang
© 2021 Meta ULC. All rights reserved